Studies on membrane biogenesis have been hampered by lack of a suitable experimental system. The Friend erythoroleukemic cell offers several advantages. Upon treatment with chemical inducers it undergoes partial differentiation in the erythoid pathway and during this process it produces hemoglobin and erythrocyte-specific membrane proteins and surface antigens. The structure and composition of the erythrocyte membrane has been extensively studied and this, in combination with an increased synthesis of erythrocyte-specifice membrane proteins by the Friend erythroleukimic cell during differentiation, makes this cell a useful system with which to study membrane biogenesis. Our objectives are to study the biosyntesis of specific erythrocyte membrane proteins during Friend mouse erythroleukemic cell differentiation, paying special attention to the site of syntesis, the intracellular transport and processing of the membrane proteins and the means by which these proteins are inserted into the plasma membrane. We shall choose for our studies those membrane proteins which undergo a marked rate of increased biosynthesis during cell differentiation with preference for asymmetric proteins such as transmembrane proteins and proteins on the tytoplasmic or outer surface of the plasma membrane.